Severe Combined Immunodeficiency (SCID)Phase 1/2BOLT+BMTNCT01852370
Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
A Phase 1/2 study testing CD3/CD19 negative allogeneic hematopoietic stem cells in people with Severe Combined Immunodeficiency (SCID) and Immunodeficiency With Predominant T-cell Defect, Unspecified, run by Paul Szabolcs at 1 site in United States.
Trial summary
The purpose of this study is to determine whether bilateral orthotopic lung transplantation (BOLT) followed by cadaveric partially-matched hematopoietic stem cell transplantation (HSCT) is safe and effective for patients aged 5-45 years with primary immunodeficiency (PID) and end-stage lung disease. Read more about this study
- Who is it for?
- Ages 5 to 45 years
- Conditions the study is for
- Severe Combined Immunodeficiency (SCID), Immunodeficiency With Predominant T-cell Defect, Unspecified, Severe Chronic Neutropenia
- What is being tested?
- CD3/CD19 negative allogeneic hematopoietic stem cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jun 2013to Nov 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subject and/or parent guardian must be able to understand and provide informed consent.
- Male or female, 5 through 45 years old, inclusive, at the time of informed consent.
- Patients must have evidence of an underlying primary immunodeficiency for which BMT is clinically indicated.
- Examples of such diseases include, but are not limited to:
- Severe Combined Immunodeficiency
- Combined immunodeficiency with defects in T-cell-mediated immunity, including Omenn syndrome and DiGeorge Syndrome
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- Severe Chronic Neutropenia
- Chronic Granulomatous Disease
- Hyper IgE Syndrome or Job Syndrome
- CD40 or CD40L deficiency
- Wiskott-Aldrich Syndrome
- Mendelian Susceptibility to Mycobacterial Disease [6]
- GATA2 Associated Immunodeficiency NOTE: A genetic diagnosis is recommended, but not required.
- Patients must have evidence of end-stage lung disease and be candidates for bilateral orthotopic lung transplant as determined by the lung transplant team.
- GFR ≥ 50 mL/min/1.73 m2.
- AST, ALT ≤ 4x upper limit of normal, total bilirubin ≤ 2.5 mg/dL, normal INR.
- Cardiac ejection fraction ≥ 40% or shortening fraction ≥26%.
- Negative pregnancy test for females >10 years old or who have reached menarche, unless surgically sterilized.
- All females of childbearing potential and sexually active males must agree to use a FDA approved method of birth control for up to 24 months after BMT or for as long as they are taking any medication that may harm a pregnancy, an unborn child or may cause birth defect.
- Subject and/or parent guardian will also be counseled regarding the potential risks of infertility following BMT and advised to discuss sperm banking or oocyte harvesting.
Who cannot join
- Individuals who meet any of these criteria are not eligible for this study:
- Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
- Patients who have underlying malignant conditions.
- Patients who have non-malignant conditions not requiring hematopoietic stem cell transplantation.
- HIV positive by serology or PCR, HTLV positive by serology.
- Females who are pregnant or who are lactating.
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- Allergy to DMSO or any other ingredient used in the manufacturing of the stem cell product.
- Uncontrolled pulmonary infection, as determined by radiographic findings and/or significant clinical deterioration. NOTE: Pulmonary colonization with multiple organisms is common, and will not be considered an exclusion criterion.
- Uncontrolled systemic infection, as determined by the appropriate confirmatory testing e.g. blood cultures, PCR testing, etc.
- Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of transplant.
- Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
- Eligibility Criteria to proceed to Bone Marrow Transplant
- GFR ≥ 50 mL/min/1.73 m2.
- AST, ALT ≤ 4x upper limit of normal, total bilirubin ≤ 2.5 mg/dL.
- Cardiac ejection fraction ≥ 40% or shortening fraction of at least 26%.
- HIV negative by serology and PCR.
- HTLV serology negative.
- FVC and FEV1 ≥40% predicted for age and SpO2 of >90% at rest on room air AND with clearance by the lung transplant team.
- Absence of uncontrolled infection as determined by positive blood cultures and radiographic progression of previous sites in particular pulmonary densities during the past 2 weeks prior to chemotherapy.
- Absence of clinically significant Acute Cellular Rejection (A2-A4 and/or B2R rejection).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
About this study
Official title: Bilateral Orthotopic Lung Transplant in Tandem With CD3+ and CD19+ Cell Depleted Bone Marrow Transplant From Partially HLA-Matched Cadaveric Donors
The purpose of this study is to determine whether bilateral orthotopic lung transplantation (BOLT) followed by cadaveric partially-matched hematopoietic stem cell transplantation (HSCT) is safe and effective for patients aged 5-45 years with primary immunodeficiency (PID) and end-stage lung disease.
Read the detailed description
This is an original IND for an investigator initiated phase I/II study. The primary purpose of the study is to evaluate the safety and efficacy of performing bilateral orthotopic lung transplantation (BOLT) followed by cadaveric, partially HLA-matched CD3+/CD19+-depleted hematopoietic stem cell transplantation (HSCT) from the same donor for patients with primary immunodeficiency diseases (PID) and end-stage lung disease. For many patients with primary immunodeficiencies, HSCT is a curative, life-saving therapy, resulting in restoration of function in the immune system. Patients with primary immunodeficiencies often develop pulmonary complications as a result of chronic or recurrent infections, making them ineligible for HSCT due to the high risk of mortality and pulmonary complications. Lung transplant prior to HSCT would allow for restoration of pulmonary function prior to HSCT, allowing PID patients to proceed to HSCT, which would be curative for the patient's underlying immunodeficiency. As a secondary aim after successful engraftment with donor bone marrow, there is realistic hope for tolerating planned withdrawal of immunosuppression achieving eventual freedom from all immunosuppressive drugs and attaining a tolerant state.
- Conditions
- Severe Combined Immunodeficiency (SCID), Immunodeficiency With Predominant T-cell Defect, Unspecified, Severe Chronic Neutropenia, Chronic Granulomatous Disease (CGD), Hyper IgE Syndromes, Hyper IgM Deficiencies
- Being tested
- CD3/CD19 negative allogeneic hematopoietic stem cells
- Keywords
- Lung transplantation, Bone Marrow Transplantation, Unrelated Donor, Cadaveric Donor, Deceased Donor, HLA-mismatch, BOLT, BMT, HSCT
- Medical subject headings
- Severe Combined Immunodeficiency, Neutropenia, severe chronic, Granulomatous Disease, Chronic, Job Syndrome, Wiskott-Aldrich Syndrome, Common Variable Immunodeficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD3/CD19 negative allogeneic hematopoietic stem cellsBiological
Negative selection for CD3/CD19 will be performed on a CliniMACS® depletion device within 36 hours of collection and given at time no less than 8 weeks post lung transplant.
| Study group | Role | What they receive |
|---|---|---|
| BOLT+BMT | Experimental | All patients will receive a double lung transplant followed by a hematopoietic stem cell transplant. The lungs and stem cells are from the same partially HLA-matched cadaveric donor. Prior to transplantation, the marrow will be negatively selected for CD3/CD19 using a CliniMACS® depletion device. Receives: Biological: CD3/CD19 negative allogeneic hematopoietic stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: Death
How many, if any, patients die.
Measured: Up to 2 years post stem cell transplant
Safety: Engraftment syndrome
How many, if any, patients develop engraftment syndrome.
Measured: Up to 2 years post stem cell transplant
Safety: Engraftment failure
How many patients, if any, develop engraftment failure.
Measured: Up to 2 years post stem cell transplant
Safety: Rituximab
The number of grade 4 and 5 events potentially related to rituximab.
Measured: Up to 2 years post stem cell transplant
Efficacy: BOS score
Bronchiolitis Obliterans Syndrome (BOS) score for all patients who receive both lungs and stem cell transplants.
Measured: 1 year post stem cell transplant
Efficacy: T-cell chimerism
The number of patients who have ≥ 25% donor T-cell chimerism.
Measured: 1 year post stem cell transplant
Efficacy: Myeloid chimerism
The number of patients with myeloid disorders (e.g. CGD) who attain ≥ 10% myeloid chimerism.
Measured: 1 year post stem cell transplant
Efficacy: B-cell chimerism
The number of patients with B-cell disorders who attain ≥ 10% B-cell chimerism.
Measured: 1 year post stem cell transplant
Secondary outcomes (14)
Feasibility of meeting BMT eligibility critieria
The number of patients who are able to proceed to BMT within 6 months following lung transplant.
Measured: Up to 2 years post stem cell transplant
Tolerance
Development of tolerance to both the host and pulmonary graft.
Measured: Up to 2 years post stem cell transplant
Long-term complications
Long-term complications of combined solid organ and BMT.
Measured: Up to 2 years post stem cell transplant
Graft failure
The number of patients who develop graft failure.
Measured: Up to 2 years post stem cell transplant
Acute cellular rejection
The number of patients who develop acute cellular rejection.
Measured: Up to 2 years post stem cell transplant
Acute graft-versus-host disease (GVHD)
The number of patient who develop acute graft-versus-host disease (GVHD).
Measured: Up to 2 years post stem cell transplant
Chronic graft-versus-host disease (GVHD)
The number of patient who develop chronic graft-versus-host disease (GVHD).
Measured: Up to 2 years post stem cell transplant
Ability to withdraw immunosuppression
The number of patients who are able to start immunosuppression withdrawal.
Measured: 1 year post stem cell transplant
Time to withdraw immunosuppression
Time from BMT to withdrawal of immunosuppression.
Measured: Up to 2 years post stem cell transplant
Pathogen-specific immunity
Time from BMT to independence from treatment dose antimicrobial drugs.
Measured: Up to 2 years post stem cell transplant
Lymphocyte count - for T-cell lymphopenias
The number of patients who are able to achieve an age adjusted, low limit normal range lymphocyte count.
Measured: 1 year post stem cell transplant
Chronic lung allograft dysfunction
The number of patients who develop chronic lung allograft dysfunction post-lung transplant for all subjects, lung only and lung+stem cell transplant.
Measured: 1 year post lung transplant
Allograft failure
The number of patients who develop allograft failure post-lung transplant for all subjects, lung only and lung+stem cell transplant.
Measured: 1 year post lung transplant
Rituximab related adverse events
The number of grade 4 or 5 adverse events possibly related to the use of rituximab.
Measured: From the time of the first dose of rituximab up to the start of BMT conditioning.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2013 (estimated)
- Study start20 Jun 2013
- Primary completionNov 2026 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Combined Immunodeficiency (SCID)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Paul Szabolcs
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Paul Szabolcs, University of Pittsburgh
- Investigators
- Paul Szabolcs, MD, Principal investigator, Division of BMT and Cellular Therapy, Children's Hospital of Pittsburgh of UPMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01852370
- Sponsor's protocol ID
- STUDY19090108
- Acronym
- BOLT+BMT
- Status last verified
- Dec 2025
- First submitted
- 26 Apr 2013
- Last updated
- 15 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bilateral Orthotopic Lung Transplant in Tandem With CD3+ and CD19+ Cell Depleted Bone Marrow Transplant From Partially HLA-Matched Cadaveric Donors
- ClinicalTrials.gov ID
- NCT01852370
- Acronym / sponsor ID
- BOLT+BMT / STUDY19090108
- Conditions
- Severe Combined Immunodeficiency (SCID), Immunodeficiency With Predominant T-cell Defect, Unspecified, Severe Chronic Neutropenia, Chronic Granulomatous Disease (CGD), Hyper IgE Syndromes, Hyper IgM Deficiencies
- Keywords
- Lung transplantation, Bone Marrow Transplantation, Unrelated Donor, Cadaveric Donor, Deceased Donor, HLA-mismatch, BOLT, BMT
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Paul SzabolcsUniversity, hospital or other
- Study start
- 20 Jun 2013 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 13 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether bilateral orthotopic lung transplantation (BOLT) followed by cadaveric partially-matched hematopoietic stem cell transplantation (HSCT) is safe and effective for patients aged 5-45 years with primary immunodeficiency (PID) and end-stage lung disease.
Detailed description
This is an original IND for an investigator initiated phase I/II study. The primary purpose of the study is to evaluate the safety and efficacy of performing bilateral orthotopic lung transplantation (BOLT) followed by cadaveric, partially HLA-matched CD3+/CD19+-depleted hematopoietic stem cell transplantation (HSCT) from the same donor for patients with primary immunodeficiency diseases (PID) and end-stage lung disease. For many patients with primary immunodeficiencies, HSCT is a curative, life-saving therapy, resulting in restoration of function in the immune system. Patients with primary immunodeficiencies often develop pulmonary complications as a result of chronic or recurrent infections, making them ineligible for HSCT due to the high risk of mortality and pulmonary complications. Lung transplant prior to HSCT would allow for restoration of pulmonary function prior to HSCT, allowing PID patients to proceed to HSCT, which would be curative for the patient's underlying immunodeficiency. As a secondary aim after successful engraftment with donor bone marrow, there is realistic hope for tolerating planned withdrawal of immunosuppression achieving eventual freedom from all immunosuppressive drugs and attaining a tolerant state.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BOLT+BMT | Experimental | Biological: CD3/CD19 negative allogeneic hematopoietic stem cellsAll patients will receive a double lung transplant followed by a hematopoietic stem cell transplant. The lungs and stem cells are from the same partially HLA-matched cadaveric donor. Prior to transplantation, the marrow will be negatively selected for CD3/CD19 using a CliniMACS® depletion device. |
Who may qualify
- Ages
- 5 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- Subject and/or parent guardian must be able to understand and provide informed consent.
- Male or female, 5 through 45 years old, inclusive, at the time of informed consent.
- Patients must have evidence of an underlying primary immunodeficiency for which BMT is clinically indicated.
- Patients must have evidence of end-stage lung disease and be candidates for bilateral orthotopic lung transplant as determined by the lung transplant team.
- GFR ≥ 50 mL/min/1.73 m2.
Key exclusion criteria (20 listed)
- Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
- Patients who have underlying malignant conditions.
- Patients who have non-malignant conditions not requiring hematopoietic stem cell transplantation.
- HIV positive by serology or PCR, HTLV positive by serology.
- Females who are pregnant or who are lactating.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD3/CD19 negative allogeneic hematopoietic stem cellsNegative selection for CD3/CD19 will be performed on a CliniMACS® depletion device within 36 hours of collection and given at time no less than 8 weeks post lung transplant. | Biological | BOLT+BMT |
Primary outcome
Safety: Death
Time frame: Up to 2 years post stem cell transplant
How many, if any, patients die.
Safety: Engraftment syndrome
Time frame: Up to 2 years post stem cell transplant
How many, if any, patients develop engraftment syndrome.
Safety: Engraftment failure
Time frame: Up to 2 years post stem cell transplant
How many patients, if any, develop engraftment failure.
Safety: Rituximab
Time frame: Up to 2 years post stem cell transplant
The number of grade 4 and 5 events potentially related to rituximab.
Efficacy: BOS score
Time frame: 1 year post stem cell transplant
Bronchiolitis Obliterans Syndrome (BOS) score for all patients who receive both lungs and stem cell transplants.
Efficacy: T-cell chimerism
Time frame: 1 year post stem cell transplant
The number of patients who have ≥ 25% donor T-cell chimerism.
Efficacy: Myeloid chimerism
Time frame: 1 year post stem cell transplant
The number of patients with myeloid disorders (e.g. CGD) who attain ≥ 10% myeloid chimerism.
Efficacy: B-cell chimerism
Time frame: 1 year post stem cell transplant
The number of patients with B-cell disorders who attain ≥ 10% B-cell chimerism.
14 secondary outcomes
Feasibility of meeting BMT eligibility critieria
Time frame: Up to 2 years post stem cell transplant
Tolerance
Time frame: Up to 2 years post stem cell transplant
Long-term complications
Time frame: Up to 2 years post stem cell transplant
Graft failure
Time frame: Up to 2 years post stem cell transplant
Acute cellular rejection
Time frame: Up to 2 years post stem cell transplant
Acute graft-versus-host disease (GVHD)
Time frame: Up to 2 years post stem cell transplant
Chronic graft-versus-host disease (GVHD)
Time frame: Up to 2 years post stem cell transplant
Ability to withdraw immunosuppression
Time frame: 1 year post stem cell transplant
Time to withdraw immunosuppression
Time frame: Up to 2 years post stem cell transplant
Pathogen-specific immunity
Time frame: Up to 2 years post stem cell transplant
Lymphocyte count - for T-cell lymphopenias
Time frame: 1 year post stem cell transplant
Chronic lung allograft dysfunction
Time frame: 1 year post lung transplant
Allograft failure
Time frame: 1 year post lung transplant
Rituximab related adverse events
Time frame: From the time of the first dose of rituximab up to the start of BMT conditioning.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paul Szabolcs, MD principal investigator
Division of BMT and Cellular Therapy, Children's Hospital of Pittsburgh of UPMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CD3/CD19 negative allogeneic hematopoietic stem cells in people with Severe Combined Immunodeficiency (SCID) and Immunodeficiency With Predominant T-cell Defect, Unspecified, run by Paul Szabolcs at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: Death (time frame: Up to 2 years post stem cell transplant). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2025.